Implantable sensor method and system

ABSTRACT

Systems and methods for non-vascular sensor implantation and for measuring physiological parameters in areas of a body where the physiological parameters are heterogeneous. An implant unit is implanted in an area of a body and a foreign body capsule is allowed to form around the implant unit area. A sensor may be directed into a body cavity such as, for example, the peritoneal space, subcutaneous tissues, the foreign body capsule, or other area. A subcutaneous area of the body may be tunneled for sensor placement. Spatially separated sensing elements may be used for detecting individual amounts of the physiological parameter. An overall amount of the physiological parameter may be determined by calculating a statistical measurement of the individual sensed amounts in the area. Another embodiment of the invention, a multi-analyte measuring device, may include a substrate having an electrode array on one side and an integrated circuit on another side.

CROSS-REFERENCE TO RELATED APPLICATIONS

Embodiments of the present invention relate to U.S. application Ser. No.10/034,627, filed Dec. 27, 2001 and U.S. Provisional Application Ser.No. 60/335,627, filed Oct. 23, 2001, each entitled “Method and Systemfor Non-Vascular Sensor Implantation,” each of which is incorporated byreference herein, and from a U.S. Provisional Application Ser. No.60/414,290, filed Sep. 27, 2002, entitled “Implantable Sensor Method andSystem,” which is also incorporated by reference herein and is a basisfor a claim of priority.

BACKGROUND

1. Field of the Invention

The present invention relates to the field of in vivo sensors and, inparticular, to in vivo sensors that are implanted in non-vascular areasof the body. The present invention also relates to a system and methodfor accurately measuring a physiological parameter in areas of a body(or external to the body) where amounts of the physiological parameterare heterogeneous in nature.

2. Description of Related Art

Traditional methods of physiological parameter sensing typically rely onvascular placement of a physiological parameter sensor. Such placementpermits a sensing element such as, for example, a biomolecule, to makedirect contact with the blood, providing sensing capabilities of bloodcomponents. Such sensing capabilities have greatly facilitated analysis,diagnosis and treatment of many debilitating diseases and medicalconditions.

However, vascular placement of a physiological parameter sensor maysuffer from several disadvantages. A physiological parameter sensor isnot inserted into a vein without great difficulty and painstaking effortby an attending physician. Moreover, a physiological parameter sensor isnot adjusted within or extracted from a vein without similar difficultyand effort.

Furthermore, vascular placement of a physiological parameter sensorsubjects the sensor to a constant fluid environment. Such an environmentmay have several detrimental effects on the sensor. Due to constantfluidic contact, the sensor may suffer from decreased sensitivity,stability and effective life. Should a characteristic of the sensor bediminished to an extent rendering the sensor ineffective, the sensormust be removed and replaced, introducing the difficulties for bothpatient and physician associated with such removal and replacement. Tocomplicate matters, every time a physiological parameter sensor isremoved and replaced, it must be disconnected and reconnected to animplant unit utilizing the sensor output.

In an effort to assuage some of the disadvantages associated withvascular implantation of physiological parameter sensors, integratedsensor/implant unit systems have been developed. Such systems may beplaced in or near a body cavity and may provide non-vascular sensing ofphysiological parameters. However, the incision required for suchsensor/implant unit systems is relatively large and the trauma in thearea of implantation can be significant. Such trauma generally preventssensing of physiological parameters. Because such trauma may not subsidefor several weeks or a month or even longer, pre-implantation analysismethods used by the patient must continue. Without continuation ofpreimplantation analysis methods, a patient may go undiagnosed anduntreated for many weeks, possibly even a month or longer. Such delay intreatment and diagnosis could be harmful or even fatal for patients whoneed daily diagnosis and treatment.

In addition, vascular implantation of physiological parameter sensorsallow the sensing elements to sense a relatively homogenous amount ofoxygen or other physiological parameter as it flows past the sensingelements. In contrast, when placing the sensor in a non-vascular area ofthe body, the physiological parameter may have a more heterogeneousnature, i.e., the amount of the physiological parameter may varysignificantly at different locations within the non-vascular area. Insuch a case, the sensing element may sense the physiological parameterthrough diffusion from, for example, fluid around the sensing element.Thus, depending on the location of the sensing element within thenon-vascular area, the amount of the physiological parameter sensed bythe sensing element may more or less accurately represent the “overallamount” of the physiological parameter within the non-vascular area,i.e., an amount that accurately represents, for example, an averageamount or other suitable statistical measure of the physiologicalparameter in the particular area of the body. In addition, anotherproblem results from the fact that the heterogeneous nature of thephysiological parameter being sensed by the sensing element may inducenoise in the signal obtained from the sensing element.

SUMMARY OF THE DISCLOSURE

Embodiments of the present invention relate to systems and methods fornon-vascular sensor implantation and to a system and method foraccurately measuring a physiological parameter in areas of a body (orexternal to the body) where amounts of the physiological parameter areheterogeneous in nature.

A method for non-vascular implant of a sensor may include implanting animplant unit in an area of a body; allowing a foreign body capsule toform around the area of the implant unit; and directing the sensor intothe foreign body capsule.

Implanting an implant unit may include incising an area of the bodylarge enough for the implant unit. Allowing a foreign body capsule toform may comprise inserting materials around the implant unit to promotegrowth characteristics. A material may be placed around the implant unitfor promoting growth characteristics. The implant unit may includeelectronics and/or a pump. The electronics may be sensor electronic orother electronics. The electronics may be integrated with the pump ormay be mutually exclusive from the pump.

The sensor may be attached to the implant unit. The sensor may beattached to the implant unit prior to formation of the foreign bodycapsule or may be attached to the implant unit subsequent to formationof the foreign body capsule.

The method may further include incising an area of the body large enoughfor the sensor. The incised area of the body large enough for the sensoris smaller than an incised area of the body large enough for the implantunit.

A method for non-vascular implant of a sensor may also include incisingan area of a body large enough for inserting an implant unit; incisingan area remote from a sensor location for inserting a sensor; directingthe sensor into a body cavity; connecting the sensor to the implantunit; and inserting the implant unit into the body. The method mayfurther include fixing the sensor in place using suture. The implantunit may be inserted into a pocket formed when incising an area of thebody large enough for inserting the implant unit.

Systems for non-vascular implant may include an implant unit fordelivering drug to a human body and a sensor for detecting aphysiological parameter. The sensor may be separate from and connectableto the implant unit and the sensor is placed in a non-vascular area ofthe human body.

The implant unit may include a pump and/or electronics. The drugdelivered by the implant unit may be insulin. The sensor may include abiomolecule, a lead and a sensing element. The sensing element may be abiomolecule and the biomolecule may be a glucose oxidase enzyme. Thephysiological parameter sensed may be oxygen or glucose. Thenon-vascular area of the human body where the sensor is placed may bethe peritoneum or subcutaneous tissue.

A plurality of spatially separated sensing elements may be used fordetecting the physiological parameter. The sensing elements may beconnectable to the implant unit. The sensing elements may be implantedin a non-vascular area of the body such that each of the sensingelements sense an individual amount of the physiological parameterwithin the area. The sensing elements may substantially simultaneouslysense individual amounts of the physiological parameter or may sense theindividual amounts in succession within a given time period. An overallamount of the physiological parameter in the area may then be determinedby employing a combination of the individual sensed amounts in astatistical analysis, such as in an algorithm or combined calculation.

The plurality of spatially separated sensing elements may be a one, two,or three-dimensional array of spatially separated sensing elements. Twoor more sensing elements may be spatially separated in a sensor lead bya pre-determined distance. The sensor lead may include a first sensingelement located at a proximal end of the sensor lead and a secondsensing element located at a distal end of the sensor lead. The sensingelements may be connected to the implant unit in a daisy chain fashion.

Each of the plurality of spatially separated sensing elements maygenerate a signal representing an individual sensed amount of thephysiological parameter. The overall amount of the physiologicalparameter may be determined by calculating a statistical measurement ofthe individual sensed amounts represented by the generated signals. Thestatistical measurement may be, but is not limited to, a maximum amountfor the individual sensed amounts, an average amount of the individualsensed amounts, a median of the individual sensed amounts, an arithmeticmean of the individual sensed amounts, a weighted arithmetic mean of theindividual sensed amounts, or the like. In this manner, a more accurateoverall measurement of the physiological parameter is possible. Inaddition, noise induced in the signals produced by the sensing elementsmay be reduced by averaging the amounts of each of the plurality ofspatially separated sensing elements.

Embodiments of the present invention may also include a method fornon-vascular implant of a sensor including incising an area of a bodylarge enough for inserting an implant unit; creating a tunnel insubcutaneous tissue; directing the sensor through the tunnel; connectingthe sensor to the implant unit; and inserting the implant unit into thebody. The tunnel may be created using a blunt instrument such as, forexample, a trocar, or other blunt instrument which minimizes trauma tothe subcutaneous tissue.

Embodiments of the present invention may also include a structure fordefining an in vivo implant site, the structure including a cylinderhaving a hollow area in an interior portion thereof, wherein a portionof the cylinder is covered with a coating. The coating may be siliconerubber and the cylinder may be a right circular cylinder. The hollowarea may be sufficiently large to accept a sensor. In addition, thecylinder may have at least one hole in an outer surface thereof.

Embodiments of the present invention may also include a multi-analytemeasuring device having a substrate, an electrode array on a first sideof the substrate, and an integrated circuit on a second side of thesubstrate. The electrode array and the integrated circuit may beelectrically connected. The integrated circuit processes signals ormonitors signals. The electrode array may include an agent, such as, forexample, an enzyme. The substrate may include channels. Themulti-analyte measuring device may also include a connector forproviding access to the integrated circuit. The connector may connect toa display device or a monitoring device. The multi-analyte measuringdevice may also include a power supply, such as, for example, a batteryor a capacitor.

These and other objects, features, and advantages of embodiments of theinvention will be apparent to those skilled in the art from thefollowing detailed description of embodiments of the invention when readwith the drawings and appended claims.

BRIEF DESCRIPTION OF THE DRAWINGS

FIG. 1 shows a general position of an implant unit and a sensor in thehuman body according to an embodiment of the present invention.

FIG. 2 shows a generalized implant unit and a sensor according to anembodiment of the present invention.

FIG. 3A shows a process for making a non-vascular placement of a sensorinto a foreign body capsule according to an embodiment of the presentinvention

FIG. 3B shows a process for making a non-vascular placement of a sensorinto a body cavity such as, for example, the peritoneal space, accordingto an embodiment of the present invention.

FIG. 3C shows a process for making a non-vascular placement of a sensorinto subcutaneous tissue according to an embodiment of the presentinvention.

FIG. 4 shows a biopsy trocar used according to an embodiment of thepresent invention.

FIG. 5A shows glucose data over a period of several days for a sensorimplanted into a foreign body capsule according to an embodiment of thepresent invention.

FIG. 5B shows glucose data over a period of several days for a sensorimplanted into subcutaneous tissue according to an embodiment of thepresent invention.

FIG. 5C shows glucose data over a period of several days for a sensorimplanted into a body cavity such as a peritoneal space according to anembodiment of the present invention.

FIG. 6 shows a blood oxygenator in which a sensing element may beplaced, according to an embodiment of the present invention.

FIG. 7 shows a sensor lead including two sensing elements according toan embodiment of the present invention.

FIG. 8 shows a graphical representation of glucose data over a period ofseveral days for each of two sensing elements of a sensor lead implantedinto the peritoneum according to an embodiment of the present invention.

FIG. 9 shows a graphical representation of the average of the glucosedata for the two sensing elements of FIG. 7 over the same periodaccording to an embodiment of the present invention.

FIG. 10 shows a graphical representation of unfiltered glucose data overa period of several days for a sensing element of a sensor leadimplanted into the peritoneum according to an embodiment of the presentinvention.

FIG. 11 shows a graphical representation of filtered glucose data forthe sensing element of FIG. 10 over the same period according to anembodiment of the present invention.

FIG. 12 shows a graphical representation of the unfiltered average ofthe glucose data for the two sensing elements of FIG. 7 over a period ofseveral days according to an embodiment of the present invention.

FIG. 13 shows a graphical representation of the filtered average of theglucose data for the two sensing elements of FIG. 7 over the same periodaccording to an embodiment of the present invention.

FIG. 14 shows a perspective view of a placement site structure accordingto an embodiment of the present invention.

FIG. 15 shows a side cutaway view of a multi-analyte sensing deviceaccording to an embodiment of the present invention.

FIG. 16 shows a top view of a multi-analyte sensing device according toan embodiment of the present invention.

FIG. 17 shows a multi-analyte sensing device and an electronicmonitoring/display device according to an embodiment of the presentinvention.

DETAILED DESCRIPTION

In the following description of preferred embodiments, reference is madeto the accompanying drawings which form a part hereof, and in which areshown by way of illustration specific embodiments in which the inventionmay be practiced. It is to be understood that other embodiments may beutilized and structural changes may be made without departing from thescope of the preferred embodiments of the present invention.

FIG. 1 shows a general placement of an implant unit 10 and a sensor 12in the human body according to an embodiment of the present invention.The implant unit 10 may be placed into a human body in a variety oflocations such as, for example, adjacent to the abdominal cavity 14, orin other locations such as, for example, the spinal cavity or chestcavity. A sensor 12 connecting to the implant unit 10 may be located inthe peritoneum 13, the membrane lining the abdominal cavity andconnecting and supporting internal organs; in subcutaneous tissue 13,i.e., tissue beneath the skin; in a foreign body capsule; or in anotherarea of the body. For example, the sensor 12 may be implanted into theshoulder area.

The implant unit 10 may contain electronics for data acquisition, datastorage, data processing or other functions as may be required forphysiological parameter sensing. In addition, the implant unit 10 mayalso contain, for example, a drug delivery system including a drugreservoir and a pumping mechanism to move a drug from the reservoir to apatient through, for example, a delivery catheter. The sensor 12 maysense a variety of physiological parameters. For example, the sensor 12may sense glucose and oxygen and may be used in connection with theimplant unit 10 to pump insulin for diabetics.

FIG. 2 shows a generalized implant unit 10 and a sensor 12 according toan embodiment of the present invention. The implant unit 10 and thesensor 12 are not integrated. They are discreet devices and may or maynot be used independently of one another. The implant unit 10 and thesensor 12 may be used in conjunction with one another and may beinserted into a patient at separate times. The ability to insert theimplant unit 10 and the sensor 12 into a patient at different timesgives physicians and patients enhanced flexibility when implanting thedevices.

As can be seen in FIG. 2, the sensor 12, according to an embodiment ofthe present invention, includes a connector 18, a sensor lead 20connected to the connector at one end, and a sensing element 22connected to the sensor lead 20 at another end. Thus, the sensingelement 22 of the sensor 12 may be located away from the implant unit 10which, as will be seen shortly, offers enhanced functionality in sensingphysiological parameters.

As shown in FIG. 2, according to an embodiment of the present inventionthe implant unit 10 may include a receptacle 16 for accepting theconnector 18 portion of the sensor 12. Also, the sensor lead 20 is notlimited to any particular length. For example, the sensor lead 20 may beapproximately nine inches long, permitting the sensing element 22 to beapproximately nine inches from the implant unit 10. However, the sensorlead 20 may be longer or shorter than nine inches depending on theapplication and the particular placement of the sensing element 22desired.

Also, the implant unit 10 may include its own lead that connects to thesensor lead 20. Thus, rather than connecting the sensor lead 20 to thereceptacle 16, the sensor lead 20 may connect to an implant unit lead.

FIG. 3A shows a process for making a non-vascular placement of thesensor 12 into a foreign body capsule according to an embodiment of thepresent invention. At step 30, a large incision may be made in the bodyat a desired or convenient location for the implant unit 10. Whilemaking the incision of step 30, a pocket may be made in the subcutaneoustissue that is large enough to support the implant unit 10. At step 32,the implant unit 10 may be inserted into the subcutaneous tissue pocket.The pocket may then be closed.

Once the implant unit 10 has been inserted into the subcutaneous tissuepocket and the pocket has been closed, the implant unit 10 may be leftin the body for a period of time long enough that a foreign body capsuleforms around the implant unit 10. The implant unit 10 may need to beleft undisturbed in its position in the body for up to several weeks, amonth, or longer in order to allow the foreign body capsule to form. Theforeign body capsule is made up of scar tissue, primarily collagen andfibrin.

During the period when the foreign body capsule is forming, a sensor 12may or may not be attached to the implant unit 10. If a sensor 12 is notattached to the implant unit 10, it may still be possible to use theimplant unit 10 in an open-loop configuration. For example, if theimplant unit 10 contains telemetry circuitry, it may be possible tocommunicate with the implant unit 10 from a remote location. Forexample, if the implant unit 10 is an insulin pump, and no sensor 12 isattached to the implant unit 10 during the period in which the foreignbody capsule is forming around the implant unit 10, the patient maystill analyze his or her insulin levels by traditional methods, such as,for example, using a home analysis system to take a blood sample andanalyze the levels of insulin in the blood. If it is determined that thepatient needs a dosage of insulin, and if the insulin pump which hasbeen placed into the patient's body is equipped with telemetryelectronics, the patient may communicate with the insulin pumptelemetrically using a portable transmitting unit and command the pumpto deliver a dosage of insulin. Thus, the patient may begin toimmediately use the insulin pump, without having a sensor 12 attached tothe pump, in an open-loop configuration. Thus, using embodiments of thepresent invention, there is no need to wait for the foreign body capsuleto form around the implant unit 10 before making use of the implant unit10.

An oxygen sensor may be used in the vicinity of the foreign body capsuleto determine if the foreign body capsule has formed and the area hashealed. Generally, no oxygen will be detected during formation of theforeign body capsule.

Once the foreign body capsule has formed around the implant unit 10, atstep 34 a small incision may be made in the vicinity of the implant unit10 pocket allowing access to the receptacle 16 of the implant unit 10.If a sensor has been previously connected to the implant unit 10, it maybe disconnected at this time. After the small incision has been made andany previously connected sensors have been disconnected from the implantunit, at step 36 the sensor 12 may be directed into the foreign bodycapsule. The sensing element 22 may be introduced into the foreign bodycapsule surrounding the implant unit through the small incision made atstep 34. The sensing element 22 may be placed within the foreign bodycapsule. The connector 18 may reside in the subcutaneous pocket createdfor the implant unit 10 by the body.

In addition, a silicone plug may be used to plug the receptacle so thatit remains open during the period of time the foreign body capsule isforming around the implant unit. If a silicone plug has been insertedinto the receptacle 16, it may also be removed at this time.

At step 38, the sensor 12 may be connected to the implant unit 10 at thereceptacle 16 on the implant unit 10 designed for connecting to thesensor 12 by connecting the connector 18 to the receptacle 16. Once thesensor 12 has been connected to the implant unit 10, the small incisionmay be closed at step 40. At this point, the implant unit 10 and thesensor 12 may be used in a closed-loop configuration. For example, ifthe implant unit 10 is an insulin pump and the sensing element 22 of thesensor 12 contains a glucose oxidase enzyme for sensing glucose andoxygen in order to determine insulin levels in the patient, the glucoseand oxygen levels and, consequently, the insulin levels in the patientmay be determined by the sensing element 22 in the foreign body capsule.Vascular placement of the sensor 12 is not required.

FIG. 3B shows a process for making a non-vascular placement of thesensor 12 into a body cavity such as, for example, the peritoneal space,according to an embodiment of the present invention. At step 50, a largeincision may be made in the body at a desired or convenient location forthe implant unit 10. While making the incision of step 50, a pocket maybe made in the subcutaneous tissue above the cavity to be used that islarge enough to support the implant unit 10.

After the large incision has been made for the implant unit 10 at step50, at step 52 a small incision may be made in a muscle wall of thecavity such as, for example, the peritoneal space, for allowingimplantation of the sensor 12. The small incision may be far or remotefrom final placement of the sensor 12. After the small incision has beenmade, at step 54 the sensor 12 may be directed into the cavity. Thesensing element 22 may be introduced into the cavity through the smallincision made at step 52. The connector 18 may reside in thesubcutaneous pocket created for the implant unit 10 by the body.

At step 56, the sensor 12 may be connected to the implant unit 10 at thereceptacle 16 on the implant unit 10 designed for connecting to thesensor 12 by connecting the connector 18 to the receptacle 16. Once thesensor 12 has been connected to the implant unit 10, at step 58 theimplant unit 10 may be inserted into the subcutaneous tissue pocketcreated at step 50. After the implant unit 10 has been inserted into thesubcutaneous tissue pocket, the pocket may be closed at step 60. Asbefore, at this point the implant unit 10 and the sensor 12 may be usedin a closed-loop configuration.

FIG. 3C shows a process for making a non-vascular placement of thesensor 12 into subcutaneous tissue according to an embodiment of thepresent invention. At step 70, a large incision may be made in the bodyat a desired or convenient location for the implant unit 10. Whilemaking the incision of step 70, a pocket may be made in the subcutaneoustissue above the cavity to be used that is large enough to support theimplant unit 10.

After the large incision has been made for the implant unit 10 at step70, at step 72 a small tunnel may be made for the sensor at the edge ofpocket created for the implant unit 10. An incision for the tunnel maybe made far or remote from final placement of the sensor 12. The tunnelmay be made using a blunt, minimally traumatic tissue implant. Thesensor 12 may be tunneled through the subcutaneous tissue by starting atan edge of the implant unit 10 pocket and tunneling into thesubcutaneous tissue parallel to the skin. It may be desirable to staywithin the subcutaneous tissue while tunneling. If the blunt, minimallytraumatic tissue implant device used includes an introducer, theintroducer may be left in the subcutaneous tissue while the remainingportion of the blunt, minimally traumatic tissue implant device may beremoved.

After the tunnel has been made, at step 74 the sensing element 22 ofsensor 12 may be directed into the introducer of the blunt, minimallytraumatic tissue implant device. The connector 18 may reside in thesubcutaneous pocket created for the implant unit 10 by the body. If itis desired that the sensor be fixed in its location, suture tabs suchas, for example, those used on pacing leads or long term catheters maybe used.

At step 76, the sensor 12 may be connected to the implant unit 10 at thereceptacle 16 on the implant unit 10 designed for connecting to thesensor 12 by connecting the connector 18 to the receptacle 16. Once thesensor 12 has been connected to the implant unit 10, at step 78 theimplant unit 10 may be inserted into the subcutaneous tissue pocketcreated at step 70. After the implant unit 10 has been inserted into thesubcutaneous tissue pocket, the pocket may be closed at step 80. Asbefore, at this point the implant unit 10 and the sensor 12 may be usedin a closed-loop configuration.

The blunt, minimally traumatic tissue implant device used to tunnel thesensor 12 into a subcutaneous region may be a biopsy trocar 90 showngenerally in FIG. 4. As shown in FIG. 4, the biopsy trocar 90 includesan introducer 92 into which the main body 94 of the trocar 90, having asharp end 100, and a secondary body 96 of the trocar 90, having a bluntend 98, may be inserted. The introducer 92 may be made of plastic whilethe main body 94 and the secondary body 96 may be made of metal. Thesecondary body 96 having the blunt end 98 may be inserted into the mainbody 94 having the sharp end 100, and both the secondary body 96 and themain body 94 may be inserted into the introducer 92. All three portionsof the trocar 90 may then be tunneled into the subcutaneous tissue. Thesharp end 100 of the main body 94 of the trocar 90 may make an initialincision, while the blunt end 98 of the secondary body 96 may tunnelthrough the subcutaneous tissue. By tunneling through the subcutaneoustissue with the blunt end 98 of the secondary body 96, less damageoccurs to the subcutaneous tissue than would occur if the subcutaneoustissue were tunneled with the sharp end 100 of the main body 94,resulting in less bleeding and less trauma to the tissue and thepatient. Once the end of the trocar 90 has reached the desired locationfor the sensing element 22 of the sensor 12, the main body 94 and thesecondary body 96 are removed from the introducer 92. The sensor 12 isthen guided through the introducer 92 so that the sensing element 22eventually arrives at its desired location. The introducer 92 may thenbe removed from the body and the connector 18 may then be connected tothe implant unit 10. Because the sensing element 22 of the sensor 12 isnot located in the vicinity of the main incision that was made to insertthe implant unit 10, the difficulties associated with obtaining a signalfrom the sensing element 22 due to the trauma of the area are avoided.Because the sensing element 22 is located away from the implant unit 10incision, there is nothing to prevent obtaining a signal from thesensing element 22 in a very short period of time. For example, afterthe sensor 12 has been tunneled into the subcutaneous tissue andconnected to the implant unit 10, it may possible to obtain a signalfrom the sensing element 22 within 24 hours of sensor 12 placement.Thus, for example, if the implant unit 10 is an insulin pump and thesensing element 22 of the sensor 12 is a glucose oxidase enzyme forsensing insulin levels in diabetics, automated insulin analysis andinsulin delivery in a diabetic patient may be feasible within 24 hoursof in vivo implantation of the implant unit 10 and the sensor 12.

If so desired, a variety of materials may be placed around the implantunit 10 or sensor 12 to promote different characteristics of the foreignbody capsule or sensor area. For example, if it is desired to grow moreblood vessels in the area of the foreign body capsule or sensor 12, theimplant unit 10 or sensor 12 may be covered with GORE-TEX or PTFE. Othermaterials may also be used to cover the implant unit 10 or sensor 12depending on the nature of the characteristics of the foreign bodycapsule or area around the sensor 12 desired. In addition, variouschemicals may be pumped into the area of the foreign body capsule inorder to promote different characteristics of the foreign body capsule,such as, for example, blood vessel growth.

The implant unit 10 and the sensor 12 are modular units and may connectto each other via a mechanical interface. Because of the modularity ofthe implant unit 10 and the sensor 12, the sensor 12 may be removed orreplaced without removing the implant unit 10. Thus, due to the smallsize of the sensor 12, only a small incision is required and trauma tothe patient is minimized. No large incision is necessary to remove theimplant unit 10 unless the implant unit 10 itself needs to be removed orreplaced.

Data for sensors used in glucose sensing applications may be seen inFIGS. 5A, 5B and 5C. In FIG. 5A, glucose data over a period of severaldays for a sensor implanted into a foreign body capsule may be seen. InFIG. 5B, glucose data over a period of several days for a sensorimplanted into subcutaneous tissue may be seen. In FIG. 5C, glucose dataover a period of several days for a sensor implanted into a body cavitysuch as a peritoneal space may be seen.

According to another embodiment of the present invention, aphysiological parameter sensing element may be placed in any medicalarticle or device that has surfaces that contact tissue, blood, or otherbodily fluids in the course of their operation, which fluids aresubsequently used in patients. This may include, for example,extracorporeal devices for use in surgery such as blood oxygenators,blood pumps, tubing used to carry blood and the like which contact bloodwhich is then returned to the patient.

FIG. 6 shows a blood oxygenator 30. Blood oxygenators are well known inthe medical field. Usually they are disposable components of so-called“heart-lung machines.” These machines mechanically pump a patient'sblood 32 and oxygenate the blood during major surgery such as a heartbypass operation. The oxygenated blood 34 is then returned to thepatient.

The physiological parameter sensing element may be placed in the bloodoxygenator 30 in order to detect oxygen or other physiologicalparameters in the patient's blood. Alternatively, the physiologicalparameter sensing element may be placed in an input line which feeds thepatient's blood 32 to the blood oxygenator 30 or an output line thatdelivers the oxygenated blood 34 to the patient. In this manner, thephysiological parameter sensing element may sense a physiologicalparameter in the blood.

Other embodiments of the present invention address the problemsdescribed above in relation to the placement of a sensor in non-vascularareas of a body. As discussed above, when the sensing element is used ina vascular area of the body, the sensing element senses an homogenousamount of oxygen or other physiological parameter as it flows past thesensing element. However, the amount of a physiological parameter innon-vascular areas of the body may be more heterogeneous. In such acase, the sensing element may sense the physiological parameter throughdiffusion from, for example, fluid around the sensing element.

Thus, when the sensing element is located in non-vascular areas of thebody, the heterogeneous nature of a physiological parameter in that areamay result in varying amounts of the physiological parameter. In otherwords, the amount of a physiological parameter sensed may vary dependingon the location of the sensing element within that particular area ofthe body. As an example, when the particular area of the body is theperitoneum and the physiological parameter is oxygen, the capillaries ofthe peritoneum are the sources of the oxygen. The topology ofcapillaries within the peritoneum may vary in different areas of theperitoneum. Thus, the oxygen levels may also vary in different areas ofthe peritoneum.

Therefore, using only one sensing element it may be difficult toaccurately determine an “overall amount” of the physiological parameterin the non-vascular areas of the body, i.e., an amount that accuratelyrepresents, for example, an average amount or other suitable statisticalmeasure of the physiological parameter in the particular area of thebody. This is because the amount of the physiological parameter may varydepending on the location of the sensing element in the particular areaof the body. In addition, another problem results from the fact that theheterogeneous nature of the physiological parameter being sensed by thesensing element may induce noise in the signal obtained from the sensingelement.

In order to more accurately determine the overall amount of thephysiological parameter in a particular area of the body and to reducethe amount of noise in the obtained signal, according to anotherembodiment of the present invention shown in FIG. 7, sensor lead 40 mayinclude two or more sensing elements. As shown in FIG. 7, one sensingelement may be a proximal sensing element 42, i.e., one located closestto an end of the sensor lead 40 that is attached to the implant unit 10.The other sensing element may be a distal sensing element 44, i.e., onelocated closest to an end of the sensor lead 40 furthest away from thepoint of attachment of the sensor lead 30 to implant unit 10. In otherembodiments, there may be further sensing elements located between theproximal sensing element 42 and the distal sensing element 44. In someembodiments, the distance between one sensing element and anothersensing element may be approximately 5 or 6 inches. However, thedistance between sensing elements may vary depending on the particularapplication in which the sensing elements are used, as well as thelocation of the sensing elements.

The spatial separation of sensing elements 42, 44 in sensor lead 40 isemployed in order to sense the physiological parameters at differentlocations within the environment in which the sensor lead 40 issituated. For example, the sensing elements 42, 44 may be situatedwithin the peritoneum and the physiological parameter to be sensed maybe oxygen. By employing two or more sensing elements that are separatedalong the sensor lead 40, each of the sensing elements may generate asignal representing an amount of oxygen at different spatial pointswithin the peritoneum. Thus, at any one time, or in succession within agiven time period, signals representing sensed amounts of oxygen may betaken from the two or more sensing elements. The individual sensedamounts of oxygen may then be used to determine an overall amount of thephysiological parameter.

This may be done, as an example, through use of an algorithm oralgorithms which determine the overall amount based on the individualsensed amounts at the different locations within the environment. Thealgorithm or algorithms, for example, may determine the overall amountof the physiological parameter by calculating a statistical measurementof the individual sensed amounts represented by the generated signals.The statistical measurement may be, but is not limited to, a maximumamount for the individual sensed amounts, an average amount of theindividual sensed amounts, a median of the individual sensed amounts, anarithmetic mean of the individual sensed amounts, or a weightedarithmetic mean of the individual sensed amounts.

The algorithm may be executed, for example, by a computing elementcomprising software, hardware, firmware or a combination of software,hardware, and firmware. In one embodiment, the computing element forexecuting the algorithm or algorithms may be implemented by electronicswithin an implant unit associated with the sensing elements 42 and 44,such as the electronics in implant unit 10 described above. Inalternative embodiments the sensing elements may be used in or with anextracorporeal device such as a blood oxygenator and the algorithm oralgorithms may be executed by a computing element associated with theextracorporeal device or by a dedicated computing element associatedwith the sensing elements.

As discussed above, the variance of oxygen levels may induce noise inthe individual sensing elements 42, 44 of the sensor lead 40. In FIG. 8,a graphical representation of glucose data over a period of several daysmay be seen for sensor lead 40 implanted into the peritoneum. Theglucose data is shown for both the proximal sensing element 42 and thedistal sensing element 44. The glucose data was obtained by detecting afirst and a second signal from the proximal sensing element 42 and thedistal sensing element 44, respectively. The first and second signalsrepresent, respectively, first and second individual amounts of glucose.As can be seen in FIG. 8, the first and second signals contain a firstand a second noise level, respectively.

In FIG. 9, a graphical representation of glucose data over the sameperiod for both the distal and proximal sensing elements is shown. Theglucose data shown in FIG. 9 is a third signal representing an averageamount of glucose calculated using the first and second signalsrepresenting individual sensed amounts of glucose. This average amountmay be calculated using an algorithm, according to an embodiment of thepresent invention described above. As can be seen in FIG. 9, an averagenoise level of the third signal (a third noise level) is less than thatof the first and second noise levels of the first and second signals,according to embodiments of the present invention. Thus, by averagingthe output signals from two or more sensing elements, the noise level ofthe averaged signal produced by the sensing elements may be reduced,producing a smoother signal. Although the statistical measurement usedto obtain the third signal above is an average amount of the individualsensed amounts, other statistical measurements may be used, including,but not limited to, a maximum amount for the individual sensed amounts,a median of the individual sensed amounts, an arithmetic mean of theindividual sensed amounts, and a weighted arithmetic mean of theindividual sensed amounts.

Although in FIG. 7 the sensing elements are shown in a one-dimensionalstraight line, the invention is not so limited. In fact, the benefit ofmultiple element spatial sensing may be realized using any geometry orarray of sensing elements, including two and three-dimensional arrays.Furthermore, multiple element spatial sensing may be performed when thesensing elements are used in a vascular area of the body and is notrestricted to use in the peritoneum or other non-vascular area.

According to embodiments of the present invention, digital signalprocessing may also be used either alone or in combination with amultiple element spatial sensing method according to embodiments of thepresent invention to reduce the noise level of the signal produced bythe sensing elements, producing a smoother signal. A digital signalprocessor (“DSP”) may use known noise reduction techniques such asfiltering, as well as other signal smoothing techniques. The DSP may belocated within an implant unit associated with the sensing elements 42and 44, such as the implant unit 10. In alternative embodiments wherethe sensing elements are used in an extracorporeal device such as ablood oxygenator, the DSP may be associated with the extracorporealdevice or may be a dedicated DSP associated with the sensing elements.

In addition, according to other embodiments of the invention, moreaggressive frequency based filtering may be used either alone or incombination with the multiple element spatial sensing and/or digitalsignal processing to reduce the noise level. Thus, the central frequencyof the noise may be determined and the filter may be used to cut off thenoise at that frequency. In one embodiment, a single-pole IIR filter isused for this purpose. However, other filters may be used depending onthe application.

In FIG. 10, a graphical representation of unfiltered glucose data over aperiod of several days may be seen for proximal sensing element 42 ofsensor lead 40 implanted into the peritoneum. In FIG. 11, a graphicalrepresentation of filtered glucose data may be seen for proximal sensingelement 42 over the same period. As can be seen in FIG. 11, the noiselevel of the signal produced by proximal sensing element 42 has beenreduced by filtering the signal according to embodiments of the presentinvention.

In FIG. 12, a graphical representation of the unfiltered average of theglucose data over the same period for both the distal and proximalsensing elements is shown. In FIG. 13, a graphical representation of thefiltered average of the glucose data over the same period for both thedistal and proximal sensing elements is shown. As can be seen in FIG.13, the noise level of the signal representing the average of theglucose data has been reduced by filtering the signal according toembodiments of the present invention.

According to other embodiments of the present invention, in vivocalibration may be used alone or in combination with the multipleelement spatial sensing, digital signal processing and/or filtering toreduce the noise level.

A placement site structure 110 used to structurally engineer a sensorplacement site according to an embodiment of the present invention isshown in FIG. 14. The placement site structure 110 may be viewed as amechanical “scaffold” within a tissue mass around which forms a vascularbed in close proximity to the sensor. A sensor (not shown in FIG. 14)may be placed within an interior space 116 of the placement sitestructure 110, providing easy sensor removal and reinsertion into anon-vascular area of the body. The placement site structure 110 may beformed into a variety of shapes to accommodate any of a variety ofsensors. In FIG. 14, the placement site structure 110 is formed as aright circular cylinder having an interior space 116. According to oneembodiment of the invention, the placement site structure 110 may be atube or a stent. In the embodiment shown, an interior diameter of theplacement site structure 110 may be 0.010″ to 0.030′ greater than anouter diameter of the sensor. A layer of silicone rubber tubing 112 maysurround the body of the placement site structure 110, except in aregion of the sensor containing an opening to an enzyme electrode. Thesilicone rubber tubing 112 may provide a barrier for tissue ingress andmay also provide direction for tissue growth between the outer surfaceof the sensor and inner surface of the placement site structure 110.Openings 114 in the placement site structure 110 may also be positionedabout 0.60″ away from a sensor electrode to facilitate tissue anchoring.Vascularization around the placement site structure 110 may be promotedby coating the silicone rubber tubing 112 with angiogenic factors orendothelial cells. Openings or holes 114 may be provided in the siliconerubber tubing 112 as an additional pathway to the implant site forangiogenic factors or plasmids which encode such factors. The size ofthe holes 114 may be in the mil or micron range. The holes 114 may alsoprovide openings for tissue ingress into the area between the sensor andthe interior walls of the placement site structure 110. Hole density andplacement may be designed to satisfy both the need for tissue growth inthe interior portion of the placement site structure 110 and the need todirect blood vessels feeding the tissue to the openings of the placementsite structure 110 closest to the sensor electrodes. The opening 114 inthe placement site structure 110 near the sensor electrodes may beexposed to an infusion of angiogenic factors, plasmids encoding forangiogenic factors, and endothelial cells. Infusion may be timed tooccur at some time after implant which is suitable for the healing ofthe implant wound to begin. Infusion of angiogenic factors, plasmidsencoding for angiogenic factors, and endothelial cells to a region closeto sensor electrodes may promote vascular growth near the active enzymeof the sensor. Angiogenic factors, plasmids encoding for angiogenicfactors, and endothelial cells may actually be incorporated within anenzyme matrix to promote blood vessel growth into the enzyme region ofthe sensor. Blood vessel density may be maximized in areas of theplacement site structure 110 not covered with a silicone rubber tubing112. Blood flow rate through any openings in the placement sitestructure 110 should be sufficient to supply the tissue growing in theinterior portion of the placement site structure 110 between theinterior walls of the placement site structure 110 and the sensor. Also,the size and spacing between anchor openings in the placement sitestructure 110 and the sensor opening may be optimized to allowsufficient analyte flux to the sensor. For sensors requiring oxygen, thesensor itself may be designed to overcome oxygen deficit through its owndesign or by its design in connection with the design of the placementsite structure 110.

Embodiments of the present invention may be used in a variety of ways.For example, embodiments of the present invention may be used inconnection with THERACYTE, INC. products. THERACYTE, INC., develops andmanufactures biocompatible medical device implants that delivertherapies for treatment of chronic and/or deficiency diseases, such as,for example, diabetes. THERACYTE, INC., implants may includebiocompatible membranes that induce the development of capillaries closeto the membranes, i.e., the implant may be vascularized. Suchvascularization promotes a supply of blood to nourish the tissues withinthe membranes. In addition, the implant may have a thin fluid layeraround a sensor placed inside of the implant or infusion site. Currentproducts available from THERACYTE, INC., include 4.5, 20 and 40microliter size implants. However, embodiments of the present inventioncan be used in connection with modifications to these products, such as,for example, implants with fewer or greater layers than the implantscurrently available from THERACYTE, INC.

Embodiments of the present invention may also be used in connection withreusable and non-reusable implant sites or sensor sites. For example,embodiments of the present invention may be used in connection withsingle or one-time implantations. As another example, embodiments of thepresent invention may be used in connection with a reusable analytesensor site for use with a replaceable analyte sensor for determining alevel of an analyte includes a site housing. The site housing materialmay be formed to have an interior cavity with an opening and a conduitthat is connected to the opening of the interior tissue ingrowth andvascularization, and yet be free of tissue ingress. Also, the sitehousing material may permit the analyte to pass through the site housingmaterial to the interior cavity, thus permitting measurement by thereplaceable analyte sensor. In addition, the conduit may have apredetermined length to inhibit trauma and encapsulation of tissueoccurring at the conduit, which is associated with placing thereplaceable analyte sensor in the interior cavity of the site housing,from interfering with the tissue ingrowth and vascularizationsurrounding the interior cavity of the site housing material. As anotherexample, embodiments of the present invention may be used in connectionwith a closed vascularized site that includes a thin layer of fluidaround the sensor, or a site that has a thin fluid layer on the interiorof the site that is used to transmit an analyte to the sensor from thevascularized site in the body. Embodiments of the invention such asthose described above are related to U.S. Pat. No. 6,368,274, ReusableAnalyte Sensor Site and Method of Using The Same, which is herebyincorporated herein by reference.

A multi-analyte measuring device 120 according to an embodiment of thepresent invention may be seen in FIGS. 15 and 16. Generally, themulti-analyte measuring device 120 includes, without limitation, asensor module 122 and a connector 124. The multi-analyte measuringdevice 120 may be used to measure a variety of analytes for diagnostics,monitoring, evaluation, or other tasks related to physiological orbiochemical parameter sensing. The multi-analyte sensing device may befabricated to be on the order of a few inches, thus making it useful ina variety of places, such as, for example, a hospital, a clinic, anambulance, a doctor's office, a residence, or even within the body of apatient. Also, depending on the desired application, the multi-analytemeasuring device 120 may be fabricated inexpensively enough such that itis disposable.

The multi-analyte measuring device 120 may be self-powered. A powersupply such as, for example, a battery or a capacitor, may be used topower the device when positioned in vivo for analyte sensing ormeasuring. The multi-analyte measuring device 120 may be located in avariety of places in vivo, including, without limitation, in anon-vascular area of the body.

The sensor module 122 may include, without limitation, an integratedcircuit 126 and an electrode array 128, as shown in FIG. 16. Theelectrode array 128 may include electrodes for sensing analytes. Theintegrated circuit 126 may address, stimulate, measure, and otherwiseoperate in connection with electrochemical events occurring at theelectrode array 128. The sensor module 122 itself may be sized accordingto its intended application. For example, according to one embodiment ofthe present invention, a diameter of the sensor module 122 is less than0.080″. According to an embodiment of the present invention, theelectrode array 128 may be in direct contact with the integrated circuit126. According to another embodiment of the present invention, theelectrode array 128 may be integral to the integrated circuit 126.

The integrated circuit 126 may be designed to facilitate a variety ofapplications. For example, according to one embodiment of the presentinvention, the integrated circuit 126 may be designed such that signalsof 1 pA can be detected at a signal-to-noise ration of 100:1. Theintegrated circuit 126 may also be provided with the capability to makepotentiometer, current and coulomb measurements, and may include signalprocessing, analog-to-digital, and electromagnetic communicationcircuitry if so desired.

The integrated circuit 126, according to an embodiment of the presentinvention, may be designed for low current or low charge detection inorder to sense low frequency electrochemical events, possibly on theorder of sub-ppm quantities for electrochemically active species of forlow pulse frequency or low duration sampling of solutions containingconcentrated electroactive species on the order of sub-ppm.

According to another embodiment of the present invention, the electrodearray 128 environment may be separated from the integrate circuitenvironment. The separation of the two environments may be facilitatedby a three-dimensional structure having an electrical connection betweenthe integrated circuit 126 and the electrode array 128, such as, forexample, a multilayer substrate. The structure or device used toseparate the two environments may be designed for complete separation ormay be designed such that the two environments are permitted toperiodically or permanently intermingle, depending on the application.

According to an embodiment of the present invention, the surface of theelectrode array 128 may be processed in a manner that impartsspecificity to detected events. The surface of the electrode array 128may include agents to impart specificity to detected events, the agentsincluding, but not limited to, antigens, labeled antigens, antibodies,labeled antibodies, enzymes, membranes, size exclusion membranes,molecularly imprinted membranes, chelating agents, haptens, and otherbiomolecules such as DNA, for example, and the like. Furthermore, theability to control electric potential as a function of time via theinteraction of the a and an agent on any specific member to theelectrode array 128 provides additional capability for enhancing thesensitivity of the multi-analyte measuring device 120.

The substrate on which the electrode array 128 resides may be processedin a manner to create one or more fluidic channels, i.e., gas or liquidchannel structures, for example, for the samples containing theanalytes. Samples may include, but are not limited to, blood, serum,urine, breath, stool, tissue, and the like. The fluid channel structuresmay be integral to the substrate containing the electrode array 128 ormay be a discrete entity. The properties of the fluid channel structuresmay depend on the amount of sample delivered to the electrode array 128.

The electrode array 128 may be processed using techniques that arecommon in the industry, such as, for example, photolithography, screenprinting, direct writing and the like. A variety or electrode array 128properties may be controlled during processing, such as for example,electrode size, spacing, geometry, relative positioning, and the like.Insulators may also be used during processing if desired, and may beused, for example, to tune sensor response. Reference and auxiliaryelectrodes may be fabricated on the substrate containing the electrodearray 128.

The multi-analyte measuring device 120 may also include a connector 124for interfacing to an electronic monitoring device or display 130 asshown in FIG. 17. The connector 124 may provide access to the integratedcircuit 126. The connector 124 may be any type of connector commonlyused in the art. The electronic monitoring device or display 130 maymonitor and/or display a variety of parameters, such as, for example,physiological or biochemical parameters or quantities.

While particular embodiments of the present invention have been shownand described, it will be obvious to those skilled in the art that theinvention is not limited to the particular embodiments shown anddescribed and that changes and modifications may be made withoutdeparting from the spirit and scope of the appended claims.

1. A method for non-vascular implant of a sensor comprising implantingan implant unit in an area of a body; allowing a foreign body capsule toform around the area of the implant unit; and directing the sensor intothe foreign body capsule.
 2. The method of claim 1, wherein implantingan implant unit comprises incising an area of the body large enough forthe implant unit.
 3. The method of claim 1, further comprising placing amaterial around the implant unit for promoting growth characteristics.4. The method of claim 1, wherein the implant unit compriseselectronics.
 5. The method of claim 1, wherein the implant unitcomprises a pump.
 6. The method of claim 1, wherein allowing a foreignbody capsule to form comprises inserting materials around the implantunit to promote growth characteristics.
 7. The method of claim 1,further comprising attaching the sensor to the implant unit.
 8. Themethod of claim 7, wherein the sensor is attached to the implant unitprior to formation of the foreign body capsule.
 9. The method of claim7, wherein the sensor is attached to the implant unit subsequent toformation of the foreign body capsule.
 10. The method of claim 1,further comprising incising an area of the body large enough for thesensor.
 11. The method of claim 10, wherein the incised area of the bodylarge enough for the sensor is smaller than an incised area of the bodylarge enough for the implant unit.
 12. A method for non-vascular implantof a sensor comprising: incising an area of a body large enough forinserting an implant unit; incising an area remote from a sensorlocation for inserting a sensor; directing the sensor into a bodycavity; connecting the sensor to the implant unit; and inserting theimplant unit into the body.
 13. The method of claim 12, whereininserting the implant unit into the body comprises inserting the implantunit into a pocket formed when incising an area of the body large enoughfor inserting the implant unit.
 14. The method of claim 12, furthercomprising fixing the sensor in place using suture.
 15. A non-vascularimplant system comprising an implant unit; a sensor for detecting aphysiological parameter, the sensor being separate from and connectableto the implant unit, wherein the sensor is placed in a non-vascular areaof the human body.
 16. The system of claim 15, wherein the implant unitcomprises a pump.
 17. The system of claim 15, wherein the implant unitcomprises electronics.
 18. The system of claim 15, wherein the implantunit delivers drug to a human body.
 19. The system of claim 18, whereinthe drug is insulin.
 20. The system of claim 15, wherein the sensorcomprises a biomolecule.
 21. The system of claim 15, wherein the sensorcomprises a lead.
 22. The system of claim 15, wherein the sensorcomprises a sensing element.
 23. The system of claim 22, wherein thesensing element is a biomolecule.
 24. The system of claim 23, whereinthe biomolecule is a glucose oxidase enzyme.
 25. The system of claim 15,wherein the physiological parameter is oxygen.
 26. The system of claim15, wherein the physiological parameter is glucose.
 27. The system ofclaim 15, wherein the non-vascular area of the human body is theperitoneum.
 28. The system of claim 15, wherein the non-vascular area ofthe human body is subcutaneous tissue.
 29. A method for non-vascularimplant of a sensor comprising: incising an area of a body large enoughfor inserting an implant unit; creating a tunnel in subcutaneous tissue;directing the sensor through the tunnel; connecting the sensor to theimplant unit; and inserting the implant unit into the body.
 30. Themethod of claim 29, wherein the tunnel is created using a bluntinstrument.
 31. The method of claim 30, wherein the blunt instrumentcauses minimal trauma to the subcutaneous tissue.
 32. The method ofclaim 30, wherein the blunt instrument is a trocar. 33-68. (canceled)69. A structure for defining an in vivo implant site comprising: acylinder having a hollow area in an interior portion thereof, wherein aportion of the cylinder is covered with a coating.
 70. The structure ofclaim 69, wherein the coating is silicone rubber.
 71. The structure ofclaim 69, wherein the cylinder is a right circular cylinder.
 72. Thestructure of claim 69, wherein the hollow area is sufficiently large toaccept a sensor.
 73. The structure of claim 69, wherein the cylinder hasat least one hole in an outer surface thereof.
 74. A multi-analytemeasuring device comprising: a substrate; an electrode array on a firstside of the substrate; and an integrated circuit on a second side of thesubstrate.
 75. The multi-analyte measuring device of claim 74, whereinthe electrode array and the integrated circuit are electricallyconnected.
 76. The multi-analyte measuring device of claim 74, whereinthe integrated circuit processes signals.
 77. The multi-analytemeasuring device of claim 74, wherein the integrated circuit monitorssignals.
 78. The multi-analyte measuring device of claim 74, wherein theelectrode array includes an agent.
 79. The multi-analyte measuringdevice of claim 78, wherein the agent is an enzyme.
 80. Themulti-analyte measuring device of claim 74, wherein the substratecomprises channels.
 81. The multi-analyte measuring device of claim 74,further comprising a connector for providing access to the integratedcircuit.
 82. The multi-analyte measuring device of claim 81, wherein theconnector connects to a display device.
 83. The multi-analyte measuringdevice of claim 81, wherein the connector connects to a monitoringdevice.
 84. The multi-analyte measuring device of claim 74, furthercomprising a power supply.
 85. The multi-analyte measuring device ofclaim 84, wherein the power supply is a battery.
 86. The multi-analytemeasuring device of claim 84, wherein the power supply is a capacitor.